RGD Reference Report - Spironolactone improves nephropathy by enhancing glucose-6-phosphate dehydrogenase activity and reducing oxidative stress in diabetic hypertensive rat.

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Spironolactone improves nephropathy by enhancing glucose-6-phosphate dehydrogenase activity and reducing oxidative stress in diabetic hypertensive rat.
Authors:	Pessoa, BS Peixoto, EB Papadimitriou, A Lopes de Faria, JM Lopes de Faria, JB
Citation:	Pessoa BS, etal., J Renin Angiotensin Aldosterone Syst. 2012 Mar;13(1):56-66. doi: 10.1177/1470320311422581. Epub 2011 Oct 10.
RGD ID:	10449128
Pubmed:	PMID:21987533 (View Abstract at PubMed)
DOI:	DOI:10.1177/1470320311422581 (Journal Full-text)
Spironolactone (SPR), a mineralocorticoid receptor blocker, diminishes hyperglycemia-induced reduction in glucose-6-phosphate dehydrogenase (G6PD) activity, improving oxidative stress damage. This study investigated whether SPR ameliorates nephropathy by increasing G6PD activity and reducing oxidative stress in spontaneously hypertensive diabetic rats (SHRs). The streptozotocin-induced diabetic rats received or not SPR 50 mg/kg per day, for eight weeks. A human mesangial cell line was cultured in normal or high glucose conditions, with or without SPR, for 24 h. Plasma glucose levels and systolic blood pressure were unaltered by diabetes or by SPR treatment. Albuminuria, fibronectin expression, 8-OHdG urinary levels, lipid peroxidation and p47phox expression were higher in the diabetic rats compared with the control and were reduced by SPR. The antioxidant GSH/GSSG ratio was reduced in the diabetic rats and the treatment reestablished it. Diabetes-induced SGK1 up-regulation was inhibited by SPR. Reactive oxygen species (ROS) and superoxide production induced by NADPH oxidase were increased by hyperglycemia and high glucose, in vivo and in vitro, respectively, and were reduced with SPR. Hyperglycemia and high glucose decreased G6PD activity, which was restored with SPR. These results suggest that SPR ameliorates nephropathy in diabetic SHRs by restoring G6PD activity and diminishes oxidative stress without affecting glycaemia and blood pressure.

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
Diabetic Nephropathies	treatment	ISO	G6pd (Rattus norvegicus)	10449128; 10449128	associated with Hypertension	RGD
Diabetic Nephropathies	treatment	IEP		10449128	associated with Hypertension	RGD

Objects Annotated

Genes (Rattus norvegicus)

G6pd (glucose-6-phosphate dehydrogenase)

Genes (Mus musculus)

G6pdx (glucose-6-phosphate dehydrogenase X-linked)

Genes (Homo sapiens)

G6PD (glucose-6-phosphate dehydrogenase)

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Spironolactone improves nephropathy by enhancing glucose-6-phosphate dehydrogenase activity and reducing oxidative stress in diabetic hypertensive rat.